For most patients with mesothelioma, symptom control and palliative chemotherapy are mainstays of care. First-line cisplatin/pemetrexed chemotherapy has demonstrated survival and quality-of-life benefits. A randomized controlled trial adding bevacizumab to cisplatin and pemetrexed recently reported improved survival and time to progression, and may constitute a new standard of care where economically viable. Immunotherapy is under active investigation and positive results have been reported from single-arm studies of the anti-CTLA4 antibody tremelimumab; the anti-PD-1 antibody pembrolizumab; and mesothelin-targeting strategies. Symptom control remains critical for patient well-being, and includes management of pleural effusion, analgesia, treatment of symptomatic masses and management of systemic symptoms. There is increasing evidence that tunneled pleural catheters are preferred over talc pleurodesis for recurrent pleural effusion.